This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. The immediate aim of this project is to determine the effect of pyrethroid insecticides on calcium homeostasis in mouse caudal epididymal sperm and the effect of these compounds on viability. Recent results indicate that voltage-sensitive calcium channels are target sites for pyrethroid insecticides. Thus, in the proposed studies at Salve Regina University, a primarily undergraduate university, the hypothesis that pyrethroid insecticides modify calcium homeostasis via modification of voltage-sensitive calcium channels will be investigated. Specifically, we will use mouse caudal epididymal sperm to examine the effects of pyrethroids on sperm motility, calcium influx, and the acrosome reaction;processes that are regulated by intracellular calcium influx via voltage-sensitive calcium channels. It is expected that pyrethroids will act as antagonists and will result in sterility due to inhibition of calcium influx via calcium channels associated with mammalian spermatozoa. A combination of behavioral and fluorescent biochemical assays in addition to more rigorous electrophysiological methods will be used to assess the effects of pyrethroids on voltage-sensitive calcium channels using mouse caudal epididymal sperm. These methods have previously been shown to be useful in the assessment of ion permeability changes induced by channel antagonists. Pyrethroids are the predominant class of insecticides used to control several medically important insects that vector human diseases. These potent insecticides have a wide spectrum of use and are effective in controlling a variety of insect pests in the prevention of insect-mediated human and animal disease transmission. The increased spread of the aforementioned diseases will likely result in increased efforts to control medically important insects and increased exposure situations for individuals in urban environments. Thus, it is critical that these insecticides be evaluated for the potential adverse effects on reproduction.